BACKGROUND Intermittent theta-burst stimulation (iTBS), a novel repetitive transcranial magnetic stimulation (rTMS) technique, appears to have antidepressant effects when applied over left dorsolateral prefrontal cortex (DLPFC). However, its underlying neurobiological mechanisms are unclear. Proton magnetic resonance spectroscopy (1H-MRS) provides in vivo measurements of cerebral metabolites altered in major depressive disorder (MDD) like N-acetyl-aspartate (NAA) and choline-containing compounds (Cho). We used MRS to analyse effects of iTBS on the associations between the shifts in the NAA and Cho levels during therapy and MDD improvement. METHODS In-patients with unipolar MDD (N = 57), in addition to treatment as usual, were randomized to receive 20 iTBS or sham stimulations applied over left DLPFC over four weeks. Single-voxel 1H-MRS of the anterior cingulate cortex (ACC) was performed at baseline and follow-up. Increments of concentrations, as well as MDD improvement, were defined as endpoints. We tested a moderated mediation model of effects using the PROCESS macro (an observed variable ordinary least squares and logistic regression path analysis modeling tool) for SPSS. RESULTS Improvement of depressive symptoms was significantly associated with decrease of Cho/NAA ratio, mediated by NAA. iTBS had a significant moderating effect enhancing the relationship between NAA change and depression improvement. CONCLUSIONS Our findings suggest a potential neurochemical pathway and mechanisms of antidepressant action of iTBS, which may moderate the improvement of metabolic markers of neuronal viability. iTBS might increase neuroplasticity, thus facilitating normalization of neuronal circuit function.

中文翻译：

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间歇性 Theta-Burst 刺激调节前扣带回 N-乙酰-天冬氨酸增加与单相抑郁改善之间的相互作用

背景间歇性theta-burst 刺激(iTBS)，一种新颖的重复经颅磁刺激(rTMS) 技术，当应用于左背外侧前额叶皮层(DLPFC) 时似乎具有抗抑郁作用。然而，其潜在的神经生物学机制尚不清楚。质子磁共振波谱 (1H-MRS) 提供了在重度抑郁症 (MDD) 中改变的大脑代谢物的体内测量，如 N-乙酰天冬氨酸 (NAA) 和含胆碱的化合物 (Cho)。我们使用 MRS 来分析 iTBS 对治疗期间 NAA 和 Cho 水平变化与 MDD 改善之间关联的影响。方法 单极 MDD 住院患者（N = 57），除了照常治疗外，随机接受 20 次 iTBS 或在 4 周内应用于左侧 DLPFC 的假刺激。在基线和随访时进行前扣带回皮层 (ACC) 的单体素 1H-MRS。浓度的增加以及 MDD 的改善被定义为终点。我们使用 SPSS 的 PROCESS 宏（观察变量普通最小二乘法和逻辑回归路径分析建模工具）测试了一个调节中介效应模型。结果 抑郁症状的改善与 NAA 介导的 Cho/NAA 比值的降低显着相关。iTBS 具有显着的调节作用，可增强 NAA 变化与抑郁症改善之间的关系。结论 我们的研究结果表明 iTBS 具有潜在的神经化学途径和抗抑郁作用机制，这可能会缓和神经元活力代谢标志物的改善。iTBS 可能会增加神经可塑性，